What’s new in hair — February 2016 | Dr. Claire A. Higgins

Distinguishing diffuse alopecia areata (AA) from pattern hair loss (PHL) using CD3+ T cells.

J Am Acad Dermatol. 2016 Feb 3. pii: S0190-9622(15)02532-3. doi: 10.1016/j.jaad.2015.12.011.

Unlike alopecia areata which is characterised by alopecic patches, diffuse subacute alopecia areata (AA) can at first glance appear to share similarities with patterned hair loss (PHL) making it difficult to diagnose.  When there is an absence of the ‘swarm of bees’, or large numbers of lymphocytes present in the peri-bulbar region, it makes it even more difficult to distinguish between diffuse AA and PHL.  In this study, Kolivras and Thompson obtained 4mm punch biopsies from 28 patients with diffuse AA, and 31 patients with PHL.  They assessed these biopsies by staining with a panel of antibodies; CD3, CD4, CD8 and CD20.  They found expression of CD3 in the peri-infundibular region of the follicle, and both the papillary and reticular dermis, in both diffuse AA and PHL.  However, CD3+ lymphocytes were found in empty follicular fibrous tracts uniquely in diffuse AA.  The authors conclude that the presence of CD3+ cells in fibrous tracts is a reliable diagnostic marker for diffuse AA, with sensitivity of 0.964, specificity of 1, and significance of <0.01.  This useful paper describes a new way for clinicians to distinguish between diffuse AA and PHL when there is a lack of peri-bulbar infiltrate to aid with diagnosis.


Frontal fibrosing alopecia severity index (FFASI): a validated scoring system for assessing frontal fibrosing alopecia.

Br J Dermatol. 2016 Feb 4. doi: 10.1111/bjd.14445.

Frontal fibrosing alopecia (FFA) is a type of hairloss characterised by progressive regression of the frontotemporal hairline.  Its’ incidence is on the rise, yet there is no standardised scoring system to categorise patients.  In this manuscript, Holmes et al propose an FFA severity index (FFASI) as a framework for patient stratification.  The score was devised to incorporate inflammatory band width, hairline recession, non-scalp hairloss and other features, with a maximum possible score of 100.  In the first incidence, 11 British Hair and Nail Society (BHNS) dermatologists were asked to use the FFASI to grade 30 FFA photographs on two separate occasions.  Intra-observer assessments showed >0.94 concordance, while inter-observer assessments showed >0.85 concordance for frontal, right lateral and left lateral hairline images.  A second evaluation was also performed in a clinical setting by 6 dermatologists.  Concordance here was <0.93 for frontal, right and left hairline, and eyebrows although it was very poor when it came to assessment of eyelashes, and other associated features.  The authors propose that FFASI be used to help standardise assessment, which will be extremely useful when evaluating the efficacy of clinical trial data for FFA.


A systematic review of pulse steroid therapy for alopecia areata.

J Am Acad Dermatol. 2016 Feb;74(2):372-374.e5. doi: 10.1016/j.jaad.2015.09.045.

Systemic pulse corticosteroids have been used for the treatment of alopecia areata since 1975.  In this article, Shreberk-Hassidim et al conducted a literature review of 41 studies, consisting of 1078 patients who have received corticosteroid treatment, either via an intramuscular, intravenous or oral mode of delivery.  With regards to efficacy, complete response was observed in 43% of the total study population, and 51% of the pediatric only studies.  Relapse in the total study population was only 17%, however in the pediatric only group is was relatively high, at 60%.  When assessing modes of delivery, intravenous/intramuscular was the most common for multifocal alopecia, at 71%, with 41% of these patients exhibiting a complete response.  In the oral steroid group (16%), 49% of study participants observed a complete response.  In ongoing studies it will be interesting to deduce wither there are epigenetic or genetic differences between responders, non-responders, and responders that relapse. This will be of use for devising patient specific treatment plans in the future.


SFRP2 augments Wnt/ β-catenin signaling in cultured dermal papilla cells.

Exp Dermatol. 2016 Feb 23. doi: 10.1111/exd.12993.

It has previously been shown that human beard dermal papillae express high levels of SFPR2, which acts to modulate Wnt activity in cells.  In this study, Kwack at al assessed SPFR2 expression in beard, occipital scalp and frontal scalp papillae, finding highest levels in the beard, and lowest in the frontal scalp.  They went on to demonstrate that the inductive potential of spheroids established using papilla cells from each site is positively correlated with SFPR2 expression; beard papilla spheroids induce the largest number of follicles in an induction assay, while frontal scalp papilla spheroids induce the least.  To determine whether SPFR2 expression is necessary for neogenesis they used an siRNA to reduce SPFR2 expression in occipital scalp papilla spheroids.   They found a significant reduction in the number of follicles the papilla cells were able to induce compared to cells containing normal levels of SFRP2.  These intriguing results point towards SFRP2 as a modulator of inductive potential in dermal papilla cells. Whether SFPR2 expression is sufficient for inductivity remains to be determined.


Hair follicle aging is driven by transepidermal elimination of stem cells via COL17A1 proteolysis.

Science. 2016 Feb 5;351(6273):aad4395. doi: 10.1126/science.aad4395.

A balance between differentiation and renewal is required for tissue homeostasis.  Too little renewal can result in atrophy and tissue decline, whereas too much can result in tissue overgrowth.  In the hair follicle, miniaturisation is commonly observed with age, and is due to a shift from the normal homeostatic balance.  In this study, Matsumura et al looked at cell and tissue dynamics in the follicle with age.  They found in both aged mouse and human hair follicles a reduction of hair follicle stem cell (HFSC) markers, but more intriguingly an almost complete loss of COL17A1, which is required for HFSC maintenance.   When they traced HSFC in aged mice they found they were leaving the follicle niche and moving to the skin epidermis, where they differentiated into skin epithelium.  The authors propose that genomic stress associated with aging results in proteolysis of COL17A1, leading to transepidermal elimination of HFSC.  When they used transgenic mice to force overexpression of COL17A1 in the hair follicle they found it prevented follicle aging.  This cutting-edge paper demonstrates that COL17A1 expression in the follicle is sufficient to prevent aging, and identifies a new therapeutic target to prevent follicle aging.


Axin2 marks quiescent hair follicle bulge stem cells that are maintained by autocrine Wnt/β-catenin signaling.

Proc Natl Acad Sci U S A. 2016 Feb 22. pii: 201601599.

Hair follicles go through cycles of active growth (anagen), regression (catagen) and rest (telogen).  During telogen, there is a bulge niche which comprises of differentiated inner bulge cells, and an outer bulge containing hair follicle stem cells.  Previously, BMP inhibitors have been detected in the Krt6+ inner bulge, believed to maintain outer bulge cells in a quiescent state during telogen.  In addition, Wnt signalling within bulge stem cells is generally thought to be inactive during telogen, coinciding with observed quiescence of these cells during this cycle stage.  In this paper, Lim et al show that contrary to popular believe, the Wnt target Axin2 is expressed in a sub-population of quiescent bulge stem cells during telogen.  When they inactivated Wnt signalling in Axin2 positive cells, follicles displayed an abnormal telogen morphology and arrested growth, showing that Wnt activity is required for Axin2 positive cells to function correctly.  They go onto demonstrate that outer bulge stem cells produce both Wnts, which can regulate the outer bulge cells in an autocrine manner, and Wnt inhibitors, which act on the inner bulge in a paracrine manner.  This adds to our understanding of the reciprocal interplay between the inner and outer bulge cells, which likely determines a number of cell fate decisions within the follicle.

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